Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first-line therapy in advanced nonsmall cell lung cancer

BACKGROUND: There is increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of the current randomized study was to evaluate the toxicity and efficacy of docetaxel plus cisplatin combination on 2 schedules in patients with previously untreated, advanced nonsmall-cell lung cancer (NSCLC). METHODS: Consenting patients with advanced NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m(2) on Day 1, plus 3-weekly (75 mg/m(2) on Day 1) or weekly (35 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle) docetaxel, for up to 6 cycles. RESULTS: Of 86 patients accrued, 41 patients were treated with 3-weekly and 43 with weekly docetaxel plus cisplatin. The most frequent grade 3/4 toxicity in the 3-weekly arm was neutropenia (56% of patients). In those receiving the weekly regimen, the frequent grade 3/4 toxicities were fatigue (44%) and nausea/vomiting (35%). The overall response rate was 40% with the 3-weekly and 39% with the weekly arm (P = .74). The median progression-free survival was 4.3 months in the 3-weekly arm and 3.9 months in the weekly arm (P = .08) and the median survival was 10.3 and 10.0 months, respectively (P = .76). Quality of life data showed no relevant difference between the arms. CONCLUSIONS: The weekly schedule of docetaxel plus cisplatin combination as first-line chemotherapy for advanced NSCLC, while feasible, has no clear advantage over the standard 3-weekly regimen.     

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.     

泰索帝每周给药联合顺铂一线治疗晚期非小细胞肺癌的临床研究

目的确定泰索帝每周给药联合顺铂治疗晚期非小细胞肺癌的最大耐受剂量（MTD）和剂量限制毒性（DLT）,观察其疗效（RR）和安全性,并进行药代动力学研究。方法泰索帝每周给药,连用3周,休息1周,顺铂每周期的第1天给药;每28d为1个治疗周期。顺铂的剂量为75mg／m^2。泰索帝在Ⅰ期临床阶段共有4个剂量组：25mg／m^2、30mg／m^2、35mg／m^2和40mg／m^2,每个剂量组至少人选3例患者。在Ⅱ期临床阶段,根据Ⅰ期临床推荐剂量,泰索帝35mg／m^2每周给药。药代动力学为第一周期第1天和第15天抽取血样待分析。根据Ⅰ期临床研究推荐剂量,进行Ⅱ期临床研究。结果Ⅰ期临床的15例患者中,有14例可评价疗效,其中5例部分缓解,有效率为35．7％,其中位生存时间16个月（范围5-40个月）。1、2、3年生存率分别为73．3％、26．6％和20．0％。中位疾病进展时间9个月（6～14个月）。Ⅱ期临床研究的83例初治的晚期非小细胞肺癌患者共接受了216个周期的化疗,可评价者75例。有1例患者完全缓解,22例患者部分缓解,占全部人组病例的27．7％（23／83）,占可评价病例的30．7％（23／75）;其中位生存时间为10．7个月（范围3—34个月）,1年生存率为48．6％。主要不良反应为Ⅲ-Ⅳ度的粒细胞减少以及乏力、指甲毒性及液体潴留。结论泰索帝（35mg／m^2）每周给药联合顺铂（75mg／m^2）作为一线方案治疗晚期非小细胞肺癌,疗效较好,骨髓毒性较小。     

低剂量持续静脉滴注吉西他滨一线治疗晚期非小细胞肺癌的临床研究

背景与目的:目前已将吉西他滨联合顺铂作为晚期非小细胞肺癌的一线化疗方案,吉西他滨的常规使用剂量和方法是1000mg/m2半小时静脉滴注,第1、8天,每3周为一个疗程。本研究旨在评价低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌的有效性和安全性。方法:48例经病理和/或细胞学检查确诊、未经化疗的晚期非小细胞肺癌患者,采用吉西他滨250mg/m2持续静脉滴注6h,第1、8天,顺铂75mg/m2,每3周为一疗程,连续使用2疗程以上。结果:48例患者中46例可评价疗效,所有患者可评价不良反应。完全缓解率2.2%,部分缓解率30.3%,总有效率为32.5%,中位治疗至进展时间为5.1个月,中位生存时间为10.2个月,1年生存率36.6%。白细胞减少发生率为60.4%,血小板减少发生率为39.5%,Ⅲ～Ⅳ度的白细胞和血小板减少发生率分别为20.8%和12.5%。结论:低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌疗效确切、不良反应轻。     

A phase II trial of weekly paclitaxel and gemcitabine in non-small cell lung cancer patients previously treated with platinum and vinorelbine

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.     

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.     

Phase II study of docetaxel and cisplatin administered as three consecutive weekly infusions for advanced non-small cell lung cancer.

Weekly administration of low-dose taxane reduces myelosuppression and increases dose intensity as compared with an every third week schedule. We conducted a phase II trial of weekly docetaxel and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) to evaluate safety and efficacy. Thirty-seven patients with chemona?ve stage IIIB (n=15), stage IV (n=16), or recurrence after operation (n=6) NSCLC received intravenous infusions of docetaxel at 35 mg/m(2) and cisplatin at 25 mg/m(2) for three consecutive weeks, followed by a week of rest. There were ten partial responses for an objective response rate of 30% (95% confidence interval (CI), 15-46%) in 33 evaluable patients and 27% (95% CI, 13-41%) in the intent-to-treatment population. The median survival was 12.8 months (range 2.5-17.1), and the 1-year survival was 54%. Hematologic toxicities, which were mild, included grade 4 neutropenia in 6%. There were none with febrile neutropenia or severe (grade 3-4) infections, and no septic deaths. The common nonhematologic toxicities included grade 2-3 nausea and vomiting (44%) and grade 2-3 diarrhea (14%). Consecutive weekly administrations of docetaxel and cisplatin for 3 weeks produces minimal myelosuppression and shows activity in the treatment of chemona?ve patients with advanced NSCLC. A randomized phase III trial is warranted to compare this 3 consecutive weeks protocol with administration of docetaxel and cisplatin every third week.     

Docetaxel (Taxotere) plus cisplatin: an active and well-tolerated combination in patients with advanced non-small cell lung cancer

The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.     

Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group.

PURPOSE: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy. PATIENTS AND METHODS: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC). RESULTS: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL. CONCLUSION: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.     

Induction Docetaxel and Cisplatin Followed by Weekly Docetaxel and Cisplatin with Concurrent Radiotherapy in Locally Advanced Stage III Non Small Cell Lung Cancer (LA-NSCLC)-A Phase II Study

Purpose: The objective of this phase II study was to document the activity and to evaluate the toxicity of docetaxel and cisplatin as induction chemotherapy followed by concurrent docetaxel and cisplatin with thoracic radiation in locally advanced stage III non small cell lung cancer. Patients and Methods: Twenty-seven patients with stage III locally advanced non-small cell lung cancer received induction chemotherapy with two cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 D1 every 3 weeks. Patients without disease progress after induction chemotherapy were assigned to concurrent chemoradiotherapy 20mg/m2 docetaxel&25mg/m2 cisplatin administrated on day 1 every week for 6 weeks along with concurrent radiotherapy at a dose of 60Gy in 30 fractions (2 Gy/fraction and 5 fractions per week). The primary endpoint was to determine the overall response rate (ORR), the secondary endpoint was to evaluate time to progression (TTP) and safety profile. Results: After induction chemotherapy, the overall response rate (ORR) was 44.4%, 23 patients without disease progress were assigned to concurrent treatment with an overall response rate of 65%. Median survival time was 17 months, time to progression was 11.5 months and the one-year survival was 58%. Neutropenia was the most common toxicity during induction therapy (26% expressed grade 3-4) whereas esophagitis was the most common toxicity during concurrent phase (17.3% expressed grade 3-4); toxicities were manageable. Conclusion: Induction chemotherapy by docetaxel and cisplatin followed by weekly docetaxel and cisplatin with concurrent thoracic radiation therapy is feasible and tolerable. These results warrant further large randomized studies to document and confirm the effectiveness of this regimen. Key Words: Lung cancer , Docetaxel , Cisplatin , Concurrent chemoradiotherapy.     

Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial

To compare the overall survival (OS) of patients with advanced non-small cell lung (NSCLC) treated with either docetaxel plus gemcitabine or single-agent docetaxel. Chemotherapy-naive patients with advanced/metastatic NSCLC were randomly assigned to receive either DG [n=157; gemcitabine 1100mg/m(2) on days 1 and 8], docetaxel 75mg/m(2) on day 8 or D [n=155; docetaxel 100mg/m(2) on day 1] every 3 weeks. A total of 312 patients were evaluable for toxicity and response. A predefined interim intention-to-treat analysis showed significantly longer median OS (p=0.037) in favor of the DG regimen (9.4 months versus 8.3 months for DG and D regimens, respectively), resulting in the premature termination of the study. The DG regimen was also associated with a significantly higher response rate compared to D (26.8% versus 11.6%, p<0.001). TTP were 3.5 and 2.3 months for the DG and D regimen, respectively (p=0.054). Although there were two treatment-related deaths in the DG arm, the toxicity profiles of the two regimens were comparable. The DG regimen was associated with a significantly better quality of life. The efficacy of the docetaxel plus gemcitabine combination is superior to single-agent docetaxel in chemonaive patients with advanced NSCLC.     

培美曲塞联合顺铂与多西他赛联合顺铂治疗晚期非小细胞肺癌的疗效比较

目的比较培美曲塞联合顺铂与多西他赛联合顺铂治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法选择我科收治的Ⅲb/Ⅳ期非小细胞肺癌患者60例,采用同期对照研究,随机分为观察组和对照组,每组30例。观察组:培养曲塞500 mg.m-2静滴,d1,顺铂25 mg.m-2静滴,d1～3;对照组:多西地赛75 mg.m-2静滴,d1,8,顺铂25 mg.m-2静滴,d1～3。每3周为1周期重复。每2周期评价疗效,直至疾病进展。结果 60例患者均可评价疗效,观察组总有效率为15.6%,疾病控制率为42.3%,中位生存期为8.9个月,1 a生存率为26.7%;对照组总有效率为13.3%,疾病控制率为40.0%,中位生存期为8.2个月,1 a生存率为23.3%,2组比较差异均无统计学意义(P均>0.05)。观察组骨髓抑制、胃肠道反应、肝功能损害等毒副反应显著低于对照组(P均<0.05)。结论培美曲塞联合顺铂治疗晚期NSCLC的疗效与多西他赛联合顺铂的疗效相近,但毒副反应明显减少,可作为晚期NSCLC患者的一线治疗用药。     

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial.

PURPOSE: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non-small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide. PATIENTS AND METHODS: The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m(2) and 250 mg/m(2)), and etoposide was given at a dose of 100 mg/m(2) daily on days 1 to 3. Each regimen was repeated every 21 days and each included cisplatin (75 mg/m(2)). RESULTS: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P =. 048). Comparing survival for the two dose levels of paclitaxel revealed no significant difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients (P =.152). For the stage IV subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P =.246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens. CONCLUSION: As a result of these observations, paclitaxel (135 mg/m(2)) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial.     

S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks. RESULTS: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%). CONCLUSIONS: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.     

国产多西他赛联合顺铂在治疗晚期非小细胞肺癌中的应用

目的:评价多西他赛(多帕菲)联合顺铂(DDP)在治疗晚期非小细胞肺癌(nonsmallcelllungcancer,NSCLC)中的疗效、毒副作用及给药方法。方法:将75例NSCLC患者随机分为3周给药方案组(38例)和周剂量方案组(37例)。3周给药方案组:多帕菲75mg/m2,d1,用药前1d开始用地塞米松(8mg,2次/d)预防过敏反应及液体潴留,连用3d;DDP25mg/m2,d1～d3,21d重复。周剂量方案组:多帕菲35mg/m2,d1、d8、d15,用药前1d开始用地塞米松(8mg,2次/d)预防过敏及液体潴留,连用3d;DDP25mg/m2,d1～d3,28d重复。至少使用2个周期后评价有效率、中位疾病进展时间(timetoprogression,TTP)、1年生存率及不良反应。结果:用多帕菲联合DDP治疗NSCLC,3周给药方案组与周剂量方案组有效率、中位TTP和1年生存率分别为47.3%∶45.9%、8.1个月∶7.8个月和44.7%∶43.2%,差异均无统计学意义,P值分别为0.902、0.631和0.896;但周剂量方案组毒副作用特别是血液学毒性较3周给药方案组明显降低,两者白细胞降低的发生率分别为86.8%和64.9%,P=0.026。结论:多帕菲联合DDP周剂量给药方案因其疗效较高而毒副作用较低是治疗NSCLC的较好方案,值得临床进一步推广应用。     

多西他赛联合替加氟和顺铂治疗晚期胃癌疗效观察

目的：观察多西他赛联合顺铂、替加氟（DCF1方案）治疗晚期胃癌的疗效和不良反应。方法：采用DCFt方案治疗66例晚期胃癌患者。多西他赛75m／m^2,d1;顺铂75m／m^2,d1;替加氟20mg／kg,静脉滴注d。天,3周1个周期,至少2个周期。结果166例晚期胃癌中,完全缓解（CR）0例,部分缓解（PR）36例（54．5％）,稳定（SD）16例（24．2％）,进展（PD）14例（21．2％）。中位肿瘤进展时间为6．1个月（3．5—11．5个月）,中位总生存期为11．2个月（6．0—14．5个月）。最常见的不良反应为骨髓抑制、消化道反应及可逆性体液潴留,不良反应多为Ⅰ-Ⅱ度,无Ⅳ度不良反应发生。骨髓抑制以自细胞减少为特点,血小板减少及贫血较轻。消化道反应主要表现为恶心呕吐、腹泻便秘。无治疗相关性死亡。结论：DCFt方案是治疗晚期胃癌安全有效的化疗方案。     

Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a combination of weekly docetaxel, gemcitabine and cisplatin in advanced transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Thirty-five chemotherapy-na?ve (adjuvant and neoadjuvant chemotherapy was allowed) patients with advanced TCC received intravenous docetaxel 35 mg/m2, gemcitabine 800 mg/m2 and cisplatin 35 mg/m2, on days 1 and 8 every 3 weeks. Prophylactic granulocyte-colony stimulating factor was given from days 3 to 6 and days 10 to 15, anti-emetics were used routinely. RESULTS: Most (27) patients (77.1%) had a performance status of 0 to 1 and eight (22.9%) had received prior adjuvant or neoadjuvant cisplatin-based chemotherapy. In the intention-to-treat analysis, the objective response rate was 65.6% [23/35 patients, 95% confidence interval (CI) 47.8% to 80.9%]. Ten patients (28.5%) achieved a complete response (95% CI 14.6% to 46.3%) and 13 (37.1%) a partial response (95% CI 21.5% to 55.0%). Median survival time was 15.5 months, median duration of response was 10.2 months and median time to progression was 8.9 months. Ten patients (28.5%) developed grade 3/4 neutropenia, including five (14.3%) who experienced febrile neutropenia, which was successfully treated. Grade 3/4 anaemia and thrombocytopenia occurred in 20% and 25.7% of patients, respectively; four patients required platelet transfusions. There were no treatment-related deaths. CONCLUSIONS: Weekly docetaxel, gemcitabine plus cisplatin is a highly effective treatment for chemotherapy-na?ve advanced TCC, and causes only moderate toxicity. This regimen should be considered as a suitable option that deserves further prospective evaluation through randomised phase III trials.     

Ⅲ期非小细胞肺癌多学科综合治疗的临床效果

目的：比较同时放化疗加巩固化疗（CCT）和同时放化疗（CRT）对Ⅲ期非小细胞肺癌的近远期疗效及不良反应.方法：57例Ⅲ期非小细胞肺癌分为2组,CRT组（28例）采用多西他赛和顺铂每周化疗同时放疗,放疗采用三维适形放疗,化疗采用多西他赛30mg/m2和顺铂20mg/m2,每周重复,共5周,CCT组（29例）先按CRT组方案治疗结束后再加用多西他赛75mg/m2和顺铂75mg/m2巩固化疗,每3周重复,共2周期.结果：CCT组和CRT组有效率分别为68.9%和53.6%,1、2、3年生存率及中位生存期CCT组分别为64.5%、36.2%、17.3%和18个月,CRT组为48.6%、21.2%、10.7%和13个月,有统计学差异.两组不良反应CCT组血液学毒性较CRT组明显.结论：Ⅲ期非小细胞肺癌患者同期放化疗后巩固性化疗可提高近期疗效、中位生存期,含紫杉类与顺铂的化疗方案可认为是最佳的选择,但其不良反应也明显增加,作为标准治疗仍需临床试验证实.     

Randomized Phase II Trial Comparing Carboplatin Plus Weekly Paclitaxel and Docetaxel Alone in Elderly Patients With Advanced Non‐Small Cell Lung Cancer: North Japan Lung Cancer Group Trial 0801

Background.

Standard first-line chemotherapy for elderly non-small cell lung cancer (NSCLC) patients has been monotherapy with vinorelbine or gemcitabine. Docetaxel has also been considered as an alternative option for the elderly population in Japan. We have previously demonstrated the high efficacy of carboplatin plus weekly paclitaxel for elderly NSCLC patients. Consequently, we conducted a randomized phase II study to select the proper regimen for a future phase III trial.

Methods.

Eligible patients were aged 70 years or older with newly diagnosed advanced NSCLC. Patients were randomly assigned either to a combination of carboplatin (area under the curve: 6 mg/mL per minute) with weekly paclitaxel (70 mg/m²) (CP regimen) or to single-agent docetaxel (60 mg/m²). The primary endpoint of this study was objective response rate. Secondary endpoints were progression-free survival, overall survival, and toxicity profile.

Results.

Among 83 eligible patients (41 to CP, 42 to docetaxel), the objective response rates were 54% (95% confidence interval: 39%–69%) and 24% (95% confidence interval: 11%–37%) and median progression-free survival was 6.6 months and 3.5 months in the CP arm and the docetaxel arm, respectively. Severe neutropenia, febrile neutropenia, and nausea were significantly frequent in the docetaxel arm, whereas toxicities in the CP arm were generally moderate. One treatment-related death was observed in the docetaxel arm.

Conclusion.

The CP regimen achieved higher activity with less toxicity than single-agent docetaxel. Considering the results of this phase II trial and the IFCT-0501 trial, we have selected the CP regimen for a future phase III trial in elderly patients with advanced NSCLC.